Interpretive Handbook

Test
9276 :
Catecholamine Fractionation, Free, 24 Hour, Urine

The catecholamines (dopamine, epinephrine, and norepinephrine) are derived from tyrosine via a series of enzymatic conversions. All 3 catecholamines are important neurotransmitters in the central nervous system and play crucial roles in the autonomic regulation of many homeostatic functions, namely, vascular tone, intestinal and bronchial smooth muscle tone, cardiac rate and contractility, and glucose metabolism. Their actions are mediated via alpha and beta adrenergic receptors and dopamine receptors, all existing in several subforms. The 3 catecholamines overlap but also differ in their receptor activation profile and consequent biological actions.

The systemically circulating fraction of the catecholamines is derived almost exclusively from the adrenal medulla, with small contributions from sympathetic ganglia. They are normally present in the plasma in minute amounts, but levels can increase dramatically and rapidly in response to change in posture, environmental temperature, physical and emotional stress, hypovolemia, blood loss, hypotension, hypoglycemia, and exercise.

In patients with pheochromocytoma, a potentially curable tumor of catecholamine producing cells of the adrenal medulla, or less commonly of sympathetic ganglia (paraganglioma), urine catecholamine levels may be elevated. This results in episodic or sustained hypertension and often in intermittent attacks of palpitations, cardiac arrhythmias, headache, sweating, pallor, anxiety, tremor, and nausea ("spells"). Elevations of the urine levels of 1 or several of the catecholamines also may be observed in patients with neuroblastoma and related tumors (ganglioneuroblastomas and ganglioneuromas) and, very occasionally, in other neuroectodermal tumors.

At the other end of the spectrum, inherited and acquired syndromes of autonomic dysfunction/failure and autonomic neuropathies are characterized by either inadequate production of 1 or several of the catecholamines, or by insufficient release of catecholamines upon appropriate physiological stimuli (eg, change in posture from supine to standing, cold exposure, exercise, stress).

This test should not be used as the first-line test for pheochromocytoma. PMET / Metanephrines, Fractionated, Free, Plasma (the most sensitive assay) and/or METAF / Metanephrines, Fractionated, 24 Hour, Urine (almost as sensitive and highly specific) are the recommended first-line laboratory tests for pheochromocytoma.

However, urine catecholamine measurements can still be useful in patients whose plasma metanephrines or urine metanephrines measurements do not completely exclude the diagnosis. In such cases, urine catecholamine specimens have an 86% diagnostic sensitivity when cut-offs of >80 mg/24 hour for norepinephrine and >20 mg/24 hour for epinephrine are employed. Unfortunately, the specificity of these cut-off levels for separating tumor patients from other patients with similar symptoms is only 88%. When more specific (98%) decision levels of >170 mg/24 hours for norepinephrine or >35 mg/24 hours for epinephrine are used, the assay’s sensitivity falls to about 77%.

Diagnosis of Neuroblastoma:

Vanillylmandelic acid, homovanillic acid, and sometimes urine catecholamine measurements on spot urine or 24-hour urine are the mainstay of biochemical diagnosis and follow-up of neuroblastoma; 1 or more of these tests may be elevated.

Many alterations in physiologic and pathologic states can profoundly affect catecholamine concentrations.

Any environmental factors that may increase endogenous catecholamine production should be avoided. These include noise, stress, discomfort, body position, and the consumption of food, caffeinated beverages, and nicotine. Caffeine and nicotine effects are short term, a few minutes to hours only.

Other substances and drugs that may affect the results include:

Substances that result in increased release or diminished metabolism of endogenous catecholamines:

-Monamine oxidase inhibitors (MOIs): a class of anti-depressants with marked effects on catecholamine levels, particularly if the patient consumes tyrosine rich foods, such as nuts, bananas, or cheese

-Catecholamine reuptake inhibitors including cocaine and synthetic cocaine derivatives, such as many local anesthetics, which also can be antiarrhythmic drugs (eg, lidocaine)